title: Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats.
abstract: OBJECTIVE
  Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested.
  
  
  METHODS
  Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days.
  
  
  RESULTS
  At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy.
  
  
  CONCLUSIONS
  Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.
authors.affiliation: Departments of Biotechnology, Urology and Nephrology Center, Mansoura University, 35516, Mansoura, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Gabr
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sobh
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Zakaria
authors.forename: Ayman F
authors.initials: AF
authors.lastname: Refaie
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ghoneim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin